Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112911 | SCV000244420 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-08-10 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0003 |
Ambry Genetics | RCV000561047 | SCV000665329 | likely benign | Hereditary cancer-predisposing syndrome | 2024-10-30 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Color Diagnostics, |
RCV000561047 | SCV000906886 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-01 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with isoleucine at codon 452 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_003665). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000496565 | SCV001363258 | uncertain significance | not specified | 2019-08-09 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.1354C>A (p.Leu452Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 247634 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1354C>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. The variant has been predicted to be benign based on multifactorial likelihood analysis (Whiley_2014). Three submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Two classified as VUS while one classified as benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Labcorp Genetics |
RCV001410482 | SCV001612531 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-12-08 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000112911 | SCV004846907 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with isoleucine at codon 452 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_003665). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Breast Cancer Information Core |
RCV000112911 | SCV000145857 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
Sharing Clinical Reports Project |
RCV000112911 | SCV000297503 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2010-11-18 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496565 | SCV000587593 | uncertain significance | not specified | 2014-01-31 | no assertion criteria provided | research |